Involvement of prostaglandin E2, cAMP, and vasopressin in lithium-induced polyuria

Sugawara, Masanori; Hashimoto, Kozo; Z, Ota

doi:10.1152/ajpregu.1988.254.6.r863

Cited by 30 publications

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“…It has been suggested that lithium acts by inhibiting adenylate cyclase activity in the collecting duct principal cells (2,5), thus preventing the production of cAMP, the second messenger for vasopressin. Prostaglandins may (6) or may not (7) play a part in this inhibition.…”

Section: Introductionmentioning

confidence: 99%

Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla.

Marples¹,

Christensen²,

Christensen³

et al. 1995

J. Clin. Invest.

408

296

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Lithium, a widely used treatment for bipolar affective disorders, often. causes nephrogenic diabetes insipidus. The effect of chronic lithium therapy on the expression of the vasopressin-regulated water channel Aquaporin-2 (AQP2) in rat kidney was examined. Membranes were prepared from inner medulla of one kidney from each rat, while the contralateral one was fixed for iminunofluorescence and immunoelectromnicroscopy. Immunoblotting revealed that lithium treatment reduced AQP2 expression dramatically, to 31±8% after 10 d and to 4±1% after 25 d, coincident with development of severe polyuria. Immunofluorescence and immunogold quantitation confirmed the lithium-induced decrease in AQP2 expression (from 11.2±1.0 to 1.1±0.2 particles/,um2). The downregulation was only partly reversed by return to lithium-free diet for 1 wk (40±8% of control). Furthermore, immunoblotting and immunogold quantitation revealed that 2 d of thirsting or 7 d of dDAVP treatment, in the continued presence of lithium, increased AQP2 expression by six-and threefold, respectively, coincident with increased urinary osmolality. Thirsting increased AQP2 immunolabeling mainly of vesicles, whereas dDAVP caused accumulation of AQP2 predominantly in the subapical region and plasma membrane. Thus, lithium causes marked downregulation of AQP2 expression, only partially reversed by cessation of therapy, thirsting or dDAVP treatment, consistent with clinical observations of slow recovery from lithium-induced urinary concentrating defects. (J. Clin. Invest. 1995. 95:1838-1845

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Section: Introductionmentioning

confidence: 99%

Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla.

Marples¹,

Christensen²,

Christensen³

et al. 1995

J. Clin. Invest.

408

296

View full text Add to dashboard Cite

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“…Not only has vasopressin been shown to stimulate prostaglandin synthesis in both collecting duct and interstitial cells, but renal prostaglandin synthesis is also increased in a variety of pathological conditions as well as during periods of dehydration (6,20,33,36). The production of prostaglandins in response to vasopressin may represent a negative feedback mechanism, since the major effect of prostaglandins on fluid balance appears to be mediated by the binding of PGE 2 to the EP 3 receptor, subsequently inhibiting increased intracellular cAMP, thereby hindering vasopressin mediated AQP2 shuttling (17,27).…”

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confidence: 99%

Dehydration-induced increase in aquaporin-2 protein abundance is blocked by nonsteroidal anti-inflammatory drugs

Baggaley

Nielsen

Marples

2010

American Journal of Physiology-Renal Physiology

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It is now well established that the antidiuretic response to vasopressin is modulated by changes in aquaporin-2 (AQP2) expression in response to hydration status. While vasopressin itself is one signal driving expression, other signals also play a part. In this study, we planned to investigate whether prostaglandins, known to modulate AQP2 trafficking, may play a role in this process. Male Wistar rats were kept in metabolic cages, with either free access to water and food, or were given 15 g of food gelled with water, such that they were fluid restricted or fluid loaded. The effects of oral administration of two structurally different NSAIDs, indomethacin and ibuprofen, and a COX-2-selective NSAID, meloxicam, on urine output and AQP2 expression were investigated in kidneys removed under terminal anesthesia. All the NSAIDs decreased AQP2 expression significantly in water-restricted rats but did not significantly alter PGE excretion. In water-loaded rats, the effects were less marked, and meloxicam had no significant effect. Consistent with this, ibuprofen prevented the increase in AQP2 expression seen in response to dehydration. These results demonstrate that NSAIDs decrease AQP2 protein abundance, particularly during adaptation during dehydration. This may be of particular significance in older and critically ill patients, who are prone to dehydration.antidiuresis; vasopressin; collecting duct IT IS NOW WELL ESTABLISHED that the acute antidiuretic action of vasopressin depends on the exocytic insertion of aquaporin-2 (AQP2) water channels from a store in intracellular vesicles to the apical plasma membrane of collecting duct principal cells (13,24,29,34), the so-called "shuttle" mechanism. Furthermore, there is now clear evidence that this acute response is modulated by changes in the total amount of AQP2 present in the cells. Such changes occur in response to chronic alterations in hydration, with water loading causing a decrease in AQP2 expression, while dehydration increases the AQP2 levels (28). Changes in AQP2 expression are also found in association with a variety of pathological conditions associated with either excess water loss (1,7,11,12,23,25) or water retention (2,30,31,39).The signals associated with changes in AQP2 expression are currently being sought. One signal is vasopressin, which causes an increase in AQP2 expression when given as a chronic infusion to either Brattleboro rats (which lack endogenous vasopressin) (5) or normal rats (8,9). This effect is thought to be mediated by cAMP and protein kinase A, which also plays a pivotal role in the acute shuttling response, via phosphorylation of a CRE-binding protein, which then binds to the promoter of the AQP2 gene (38). However, it is now clear that vasopressin-independent pathways also play a role, since decreases in AQP2 are seen in association with the ability to lose water in the urine despite ongoing vasopressin infusion (vasopressin escape phenomenon) (8, 9). This escape phenomenon has been shown to depend on both nitric oxide and prostagl...

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“…In animal models, Li-induced polyuria is associated with decreased protein abundance of AVP-regulated collecting duct water channel aquaporin (AQP)2 (31,36). The AVP resistance in Li-induced NDI has been attributed to increased production of renal prostaglandin (PG)E 2 (48). PGE 2 is a potent antagonist of AVP action on collecting duct (19,40,44,56).…”

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confidence: 99%

Potential role of purinergic signaling in lithium-induced nephrogenic diabetes insipidus

Zhang

Nelson²,

Carlson³

et al. 2009

American Journal of Physiology-Renal Physiology

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Zhang Y, Nelson RD, Carlson NG, Kamerath CD, Kohan DE, Kishore BK. Potential role of purinergic signaling in lithiuminduced nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 296: F1194 -F1201, 2009. First published February 25, 2009 doi:10.1152/ajprenal.90774.2008.-Lithium (Li)-induced nephrogenic diabetes insipidus (NDI) has been attributed to the increased production of renal prostaglandin (PG)E2. Previously we reported that extracellular nucleotides (ATP/UTP), acting through P 2y2 receptor in rat medullary collecting duct (mCD), produce and release PGE2. Hence we hypothesized that increased production of PGE 2 in Li-induced NDI may be mediated by enhanced purinergic signaling in the mCD. Sprague-Dawley rats were fed either control or Li-added diet for 14 or 21 days. Li feeding resulted in marked polyuria and polydipsia associated with a decrease in aquaporin (AQP)2 protein abundance in inner medulla (ϳ20% of controls) and a twofold increase in urinary PGE2. When acutely challenged ex vivo with adenosine 5Ј-O-(3-thiotriphosphate) (ATP␥S), UTP, or ADP, mCD of Li-fed rats showed significantly higher increases (50 -130% over control diet-fed rats) in PGE 2 production, indicating that more than one subtype of P 2y receptor is involved. This was associated with a 3.4-fold increase in P2y4, but not P2y2, receptor mRNA expression in the inner medulla of Li-fed rats compared with control diet-fed rats. Confocal laser immunofluorescence microscopy revealed predominant localization of both P2y2 and P2y4 receptors in the mCD of control or Li diet-fed rats. Together, these data indicate that in Li-induced NDI 1) purinergic signaling in the mCD is sensitized with increased production of PGE2 and 2) P2y2 and/or P2y4 receptors may be involved in the enhanced purinergic signaling. Our study also reveals the potential beneficial effects of P 2y receptor antagonists in the treatment and/or prevention of Li-induced NDI. collecting duct; P 2 receptors; extracellular nucleotides; prostaglandin E 2; cyclooxygenases; bipolar disorder; neurodegeneration; rat LITHIUM (Li) has been in clinical use for about half a century, mostly for the treatment of bipolar disorder, which affects up to 2% of the US population (33), with double the incidence in veterans. Mental depression and substance abuse, which are often encountered in posttraumatic stress disorder patients, such as war veterans, are known to predispose them to bipolar disorders. Despite the advent of newer drugs for bipolar disorders, Li is still an important medication in the psychiatric treatment regimen by virtue of the significantly lower suicidal risk in Li-treated patients (3). In addition, the advances in the pharmacotherapeutics of bipolar disorder over the past 10 -15 yr have been predominantly in terms of tolerability and safety, with no new treatments being demonstrated to be more effective than Li (38). Furthermore, recent studies unraveled the neuroprotective effect of Li, thus making it a potential drug for the treatment of acute brain injury (e.g., stroke...

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Involvement of prostaglandin E2, cAMP, and vasopressin in lithium-induced polyuria

Cited by 30 publications

References 0 publications

Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla.

Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla.

Dehydration-induced increase in aquaporin-2 protein abundance is blocked by nonsteroidal anti-inflammatory drugs

Potential role of purinergic signaling in lithium-induced nephrogenic diabetes insipidus

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